A Toll-Spätzle pathway in the tobacco hornworm, Manduca sexta

► Manduca sexta Toll interacts with MsSpz-C108 (the active C-terminal domain of Spz) but not with full-length MsSpz. ► Co-expression of MsToll with MsSpz-C108 but not MsSpz activates drosomycin in Drosophila S2 cells. ► Activation of AMP genes in M. sexta larvae by MsSpz-C108 is blocked by antibody to MsToll. ► Activation of M. sexta AMP genes by Lys-type and DAP-type peptidoglycans is blocked by antibody to MsToll. ► Both in vitro and in vivo results demonstrate a Toll-Spz pathway in M. sexta, a lepidopteran insect.